Proteins and other markers are important factors in disease states. A “marker” typically refers to a molecule such as a polypeptide, which alone or in combination with other markers, differentiates one biological state from another. For example, proteins can vary in association with changes in biological states such as disease. When disease strikes, some proteins become dormant, while others become active. Prostate Specific Antigen (PSA), for example, is a circulating serum protein that, when present in elevated concentrations, correlates with prostate cancer. When markers such as PSA are identified, they can be used as diagnostic tools or can be used to identify drugs that can be used to address the diseases associated with the markers.
Surface-enhanced laser desorption/ionization processes have been used to identify biomarkers. “Surface-enhanced laser desorption/ionization” or “SELDI” refers to a method of desorption/ionization gas phase ion spectrometry (e.g., mass spectrometry) in which an analyte (e.g., a protein) is captured at a sample spot of a SELDI probe that engages a probe interface of the gas phase ion spectrometer. In “SELDI MS,” the gas phase ion spectrometer is a mass spectrometer. SELDI technology is described in, e.g., U.S. Pat. No. 5,719,060 (Hutchens and Yip) and U.S. Pat. No. 6,225,047 (Hutchens and Yip). A laser desorbs the captured analyte (e.g., a protein) from the surface of the probe and the desorbed analyte is received at a detector. A material called an “EAM” or energy absorbing material is at the sample spot and absorbs some of the laser energy during the desorption process.
After detection, the time of flight (TOF) of the desorbed analyte is determined. Each time-of-flight value is converted into a mass-to-charge ratio, or M/Z. TOF-to-M/Z transformation involves the application of an algorithm that transforms times-of-flight into mass-to-charge ratios (M/Z). In this step, the signals are converted from the time domain to the mass domain. After the proteins are desorbed and detected, and M/Zs are determined, a mass spectrum like the one shown in FIG. 1 is produced by the mass spectrometer.
As shown in FIG. 1, the y-axis is a measure of signal intensity while the x-axis represents a specific mass-to-charge ratio. A high signal intensity at a particular mass-to-charge ratio indicates a high concentration of a substance with that mass-to-charge ratio. In FIG. 1, the peak at about 27,000 represents a particular substance at that mass-to-charge ratio.
Spectra created under similar processing conditions can be separately grouped and then analyzed. For example, two mass spectra can be created using the same laser energy and wash conditions, but may be respectively derived from diseased and non-diseased samples. The two mass spectra may have different signal intensities (or “peaks”) at a given mass-to-charge ratio. A substance at that particular mass-to-charge ratio can be characterized as being “differentially expressed” in the two samples, and the particular substance may be a marker for the particular diseased state that is being investigated.
Surface-enhanced laser desorption/ionization data is multi-dimensional and can include specific processing values such as type of energy absorbing material (EAM) used, the particular laser energy used, the type of adsorbent used, etc. One strength of the surface-enhanced laser desorption/ionization process includes the ability to identify markers such as proteins by analyzing a sample with a variety of different surface chemistries and different sample preparation steps.
With the increasing use of automated processing, even more spectra can be created than can be manually organized, processed, or analyzed by users. High throughput collection and analysis of such multi-dimensional surface-enhanced laser desorption/ionization data requires better data management systems than are presently available.
Embodiments of the invention address these and other problems.